It is well known that studies are conducted in animals during preclinical drug development to determine in vivo pharmacokinetics, pharmacodynamics, efficacy, and toxicity, and that these studies are used in an effort to predict effective drug concentrations in humans. Advancements in small-animal imaging technology over the past decade have enabled quantitative assessment of dynamic in vivo distribution of radiolabeled compounds (Smith-Jones et al., Nature Biotechnol. 22:701-706, 2004; Robinson et al., Cancer Res. pp. 1471-1478, 2005; Cai et al., Eur. J. Nucl. Med. Mol. Imaging 34:850-858, 2007; Cai et al., J. Nucl. Med. 48:304-310, 2007; Sosabowski et al., Star 40:2082-2089, 2009) as well as quantitative sub-organ analysis (Hoppin et al., J. Pharmacol. Exp. Ther. In press). Designing, performing, and interpreting these imaging studies is a complex, interdisciplinary effort. Many parameters define the results of an imaging study including isotope selection, radiolabeling chemistry, specific activity, injected activity, compound pharmacology, the animal model, imaging time points, imaging scan time, reconstruction algorithms, image processing, and others.
In the clinic, molecular imaging (primarily SPECT and PET) is a medical imaging technique in which a human subject can be imaged in two- or three-dimensions to quantitatively or semi-quantitatively determine the distribution of an administered exogenous contrast agent.
Existing approaches to analysis of PET and SPECT in the clinic include drawing regions of interest and determining the concentration or relative concentration of the contrast agent in the region of interest. However, it is unclear how the concentration of contrast agent is related to contrast agent and in vivo transport properties.